Rates and types of infections in left ventricular assist device recipients: A scoping review

Abstract

Central MessageThis scoping review found that most studies of infections in LVAD recipients did not utilize standardized infection definitions and did not complete information on infection locations and types.PerspectiveIn this scoping review of 132 studies reporting infections in LVAD recipients, most studies did not use standardized infection definitions and most studies did not report complete demographic information. To advance the scientific rigor of investigations into infections in LVAD recipients, future studies should use standardized definitions and meet minimum reporting guidelines.See Commentaries on Pages 412, 414, and 416. This scoping review found that most studies of infections in LVAD recipients did not utilize standardized infection definitions and did not complete information on infection locations and types. In this scoping review of 132 studies reporting infections in LVAD recipients, most studies did not use standardized infection definitions and most studies did not report complete demographic information. To advance the scientific rigor of investigations into infections in LVAD recipients, future studies should use standardized definitions and meet minimum reporting guidelines. See Commentaries on Pages 412, 414, and 416. Use of left ventricular assist devices (LVADs) has increased over time as the number of patients with end-stage heart failure increases relative to the availability of heart transplant donor organs. Although outcomes in LVAD recipients have improved with advances in technology, infections remain a persistent problem and are the most common adverse event after LVAD implantation.1Molina E.J. Shah P. Kiernan M.S. Cornwell III, W.K. Copeland H. Takeda K. et al.The Society of Thoracic Surgeons Intermacs 2020 annual report.Ann Thorac Surg. 2021; 111: 778-792Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Infections associated with LVAD implantation remain a persistent problem and are the most common adverse event during the first year after LVAD implantation, with only 59% of patients free from major infection at 1 year after implant.1Molina E.J. Shah P. Kiernan M.S. Cornwell III, W.K. Copeland H. Takeda K. et al.The Society of Thoracic Surgeons Intermacs 2020 annual report.Ann Thorac Surg. 2021; 111: 778-792Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Although there are several subtypes of infections in LVAD recipients (eg, driveline infection, bacteremia, pneumonia, and urinary tract infection), all of them have been linked to an increased risk of postimplant complications (eg, rehospitalization, need for device exchange, stroke, or death) as well as associated increased expenditures.2Akhter S.A. Badami A. Murray M. Kohmoto T. Lozonschi L. Osaki S. et al.Hospital readmissions after continuous-flow left ventricular assist device implantation: incidence, causes, and cost analysis.Ann Thorac Surg. 2015; 100: 884-889Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 3Shah P. Birk S.E. Cooper L.B. Psotka M.A. Kirklin J.K. Barnett S.D. et al.Stroke and death risk in ventricular assist device patients varies by ISHLT infection category: an INTERMACS analysis.J Heart Lung Transplant. 2019; 38: 721-730Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 4Hannan M.M. Xie R. Cowger J. Schueler S. de By T. Dipchand A.I. et al.Epidemiology of infection in mechanical circulatory support: a global analysis from the ISHLT Mechanically Assisted Circulatory Support Registry.J Heart Lung Transplant. 2019; 38: 364-373Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar Despite the burden of infections in LVAD recipients, existing literature investigating this complication are mostly limited to small, single-center observational series. In addition, existing systematic reviews have focused on a limited number of infection subtypes rather than comprehensively studying all infection subtypes among patients receiving contemporary LVADs.5O'Horo J.C. Saleh O.M.A. Stulak J.M. Wilhelm M.P. Baddour L.M. Sohail M.R. Left ventricular assist device infections: a systematic review.ASAIO J. 2018; 64: 287Crossref PubMed Scopus (51) Google Scholar This gap in this literature limits generalizability and application of the findings. The objectives of this scoping review were to synthesize published evidence related to rates of different types of infections in LVAD recipients to report clinical trial and real-world infection rates, identify research gaps, and highlight methodological concerns to improve future studies. This scoping review is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews guidelines (Appendix 1).6Tricco A.C. Lillie E. Zarin W. O'Brien K.K. Colquhoun H. Levac D. et al.PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation.Ann Intern Med. 2018; 169: 467-473Crossref PubMed Scopus (4177) Google Scholar Using existing literature among patients receiving LVAD, this study evaluated rates and types of infections and risk factors, including patient characteristics, processes of care, and device characteristics. A scoping review methodology was selected rather than a systematic review due to lack of high-quality studies addressing the research questions and large variability in study designs, definition of infections, and study methods.7Munn Z. Peters M.D.J. Stern C. Tufanaru C. McArthur A. Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach.BMC Med Res Methodol. 2018; 18: 143Crossref PubMed Scopus (1436) Google Scholar Accordingly, this study included randomized trials, cohort, case control studies, case reports, and case series. The following electronic databases were searched between January 2006 to February 2019 to include contemporary LVADs: PubMed.gov, Scopus, Embase (including Embase Classic), Cumulative Index to Nursing and Allied Health Literature Complete (EbscoHost), and Web of Science Core Collection [Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Arts & Humanities Citation Index (A&HCI), Conference Proceedings Citation index - Science (CPCI-S), Conference Proceedings Citation Index - Social Science & Humanities (CPCI-SSH), Book Citation Index - Science (BKCI-S), Book Citation Index - Social Science & Humanities (BKCI-SSH), Emerging Sources Citation Index (ESCI), Current Chemical Reactions (CCR-EXPANDED)]. References of all included articles as well as narrative and systematic reviews were reviewed to ensure inclusion of all pertinent articles. There were no other restrictions. Search key words were compiled by 3 authors (S.S., T.W., and W.T.) using the population (adult patients with a durable LVAD), concept (LVAD infections), and context (risk factors for infection) approach to designing scoping review search strategy.7Munn Z. Peters M.D.J. Stern C. Tufanaru C. McArthur A. Aromataris E. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach.BMC Med Res Methodol. 2018; 18: 143Crossref PubMed Scopus (1436) Google Scholar (Appendix 2). Deduplication was performed using Covidence systematic review software (Veritas Health Information, Melbourne, Australia). Three authors (S.S., T.W., and D.L.) independently assessed the title and abstract of each item identified in the initial search to determine suitability for full-text review. At this stage, all studies were included if the study population was aged 18 years and older and received a durable continuous-flow LVAD. Any article deemed appropriate by either author was advanced to the next stage. Next, 4 independent authors (S.S., T.W., G.Y., and D.L.) reviewed the full text of selected articles to only include studies meeting the inclusion criteria listed below. Each full-text article was reviewed by 2 authors and disagreements were resolved by a third author. The criteria for inclusion for analysis were:•Adults aged 18 years or older;•Contemporary LVADs used in the United States (HeartMate II [Abbott, Abbott Park, Ill], HeartMate 3 [Abbott], and HeartWare HVAD [Medtronic, Minneapolis, Minn). If the study included other LVADs but infections were specified for LVADs of interest, it was included;•Published full-text article in English language available for review;•Studies with at least 10 patients; and•Described rate of any infection and/or looked at predictors of infection in LVAD recipients. The criteria for exclusion were:•All narrative and systematic reviews, editorials, or study protocols; and•If details on LVAD type studied were not provided. Four independent authors (S.S., M.P., G.Y., and D.L.) extracted data from selected full-text articles for review. A review form was developed and utilized to collect prespecified elements from each study (Appendix 3). Extracted information included author names, study design, country of origin, study population, patient demographic characteristics, follow-up duration, infections subtypes and rates, use of standardized infection definitions as per the International Society for Heart and Lung Transplantation (ISHLT) Consensus Statement.8Hannan M.M. Husain S. Mattner F. Danziger-Isakov L. Drew R.J. Corey G.R. et al.Working formulation for the standardization of definitions of infections in patients using ventricular assist devices.J Heart Lung Transplant. 2011; 30: 375-384Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar Each article was reviewed independently by 2 authors and disagreements were resolved through discussion with involvement of a third author to arrive at consensus. Analyses were descriptive and displayed in tabular or graphical formats. Summary statistics were generated where appropriate using Stata IC (StataCorp, College Station, Tex). Frequency and percentage were reported for categorical variables and median with interquartile range (IQR) were reported for continuous variables. Results were displayed with tables, a bar chart, and a box plot. A variety of study designs and end points were included so outcomes and results were not pooled. After screening 9680 titles and abstracts for eligibility, and reviewing 480 full texts, 132 full texts were included for data extraction (Figure 1). The study characteristics are described in Table 1. References for all studies meeting inclusion criteria included are summarized in Appendix 4.Table 1Study characteristicsCharacteristicResultCountry of origin United States88/132 (66.7) Germany11/132 (8.3) Multiple10/132 (7.6) Japan5/132 (3.8) Turkey5/132 (3.8) United Kingdom3/132 (2.3) Italy2/132 (1.5) Netherlands2/132 (1.5) Canada2/132 (1.5) Denmark2/132 (1.5) Kazakhstan1/132 (0.7) Singapore1/132 (0.7)Study design Observational118/132 (89.4) Randomized4/132 (3.0) Interventional, non-randomized10/132 (7.6)Use of ISHLT infection classification48/132 (36.4)Pathogen reported22/132 (16.7)Follow-up duration reported93/132 (69.7)Patient age reported97/132 (73.5)Patient sex reported119/132 (90.2)Patient race reported33/132 (25)Device type HVAD134.5 (70-268.5) (n = 96 studies) HMII44 (19-123) (n = 44 studies) HM350 (12.5-101) (n = 12 studies)Values are presented as n/n (%) or median (interquartile range). ISHLT, International Society for Heart and Lung Transplantation; HVAD, HeartWare HVAD (Medtronic, Minneapolis, Minn); HMII, HeartMate II (Abbott, Abbott Park, Ill); HM3, HeartMate 3 (Abbott). Open table in a new tab Values are presented as n/n (%) or median (interquartile range). ISHLT, International Society for Heart and Lung Transplantation; HVAD, HeartWare HVAD (Medtronic, Minneapolis, Minn); HMII, HeartMate II (Abbott, Abbott Park, Ill); HM3, HeartMate 3 (Abbott). The majority of studies were conducted in the United States (n = 88 [66.7%]), followed by Germany (n = 11 [8.3%]). Studies were identified from 11 different countries with 11 studies reporting data from multiple countries. Most studies were observational (n = 118 [89.4%]) and were conducted at a single institution (n = 93 [70.4%]). A total of 72 identified unique patient cohorts were represented in this report (Appendix 5). The number of patients per study ranged from 16 to 1064 with a median of 137 (IQR, 60-282). The gender distribution was provided in 119 (90.1%) studies, with men representing the majority (median proportion, 79.3%; IQR, 75.0%-83.3%) in most studies. The racial distribution was reported in 33 studies with White patients representing the majority (median proportion, 68.1%; IQR, 55.4%-74.5%) of the population. Follow-up duration was included in 93 studies (67.9%). The most commonly studied device was HeartMate II (96 studies; median number of devices, 134.5; IQR, 70-268.5) followed by HeartWare (70 studies; median number of devices, 44; IQR, 19-123) and HeartMate 3 (12 studies; median number of devices, 50; IQR, 12.5-101). The number of articles related to LVAD infection published per year increased over time from 1 in 2007 to 39 in 2018 (Figure 2). Most studies did not utilize standardized infection definitions, with only 48 (36%) using ISHLT definitions. The number of articles using ISHLT definitions steadily increased over time after 2011 with 58% studies in 2017 using standardized definitions (Figure 2). The most commonly studied LVAD-specific infections were driveline infections (98 studies) followed by pocket infections (20 studies) and pump or cannula infections (3 studies). Driveline infection incidence for the entire cohort was reported in 92 studies with the number of patients ranging from 16 to 1064 (median, 123; IQR, 55.5-248). For studies reporting infection rates within the first 30 days of LVAD implant, the incidence ranged from 0% to 2.6%. Reported driveline infection rates ranged from 5.0% to 56% within the first 6 months postimplant, 7% to 71% at 1 year, and 7% to 65% at 2 years. In studies using standardized definition for infections in LVAD recipients provided by ISHLT, variation in rates of driveline infection persisted (Figure 3). The incidence of pocket infections was reported in 20 studies, although the number of patients per study ranged from 28 to 414 (median, 139; IQR, 96-273.5). The reported incidence of pocket infections within the first month postimplant was 0%,9Gregoric I.D. Radovancevic R. Akay M.H. Jezovnik M.K. Nathan S. Patel M. et al.Short-term experience with off-pump versus on-pump implantation of the HeartWare left ventricular assist device.ASAIO J. 2017; 63: 68-72Crossref PubMed Scopus (7) Google Scholar 0% to 2% within the first 6 months,10Miller L.W. Pagani F.D. Russell S.D. John R. Boyle A.J. Aaronson K.D. et al.Use of a continuous-flow device in patients awaiting heart transplantation.N Engl J Med. 2007; 357: 885-896Crossref PubMed Scopus (1343) Google Scholar,11Pagani F.D. Miller L.W. Russell S.D. Aaronson K.D. John R. Boyle A.J. et al.Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device.J Am Coll Cardiol. 2009; 54: 312-321Crossref PubMed Scopus (701) Google Scholar 0.4% to 10% at 1 year,12Ertugay S. Engin C. Nalbantgil S. Kocabaş S. Balcioglu O. Engin Y. et al.Postoperative outcomes of the largest HeartMate-II experience in Turkey.Transplant Proc. 2015; 47: 1499-1502Crossref PubMed Scopus (1) Google Scholar,13Cagliostro B. Levin A.P. Fried J. Stewart S. Parkis G. Mody K.P. et al.Continuous-flow left ventricular assist devices and usefulness of a standardized strategy to reduce drive-line infections.J Heart Lung Transplant. 2016; Full Text Full Text PDF PubMed Scopus Google Scholar and 0% to at 2 A.C. S. S. experience with implantation of HeartMate II left ventricular assist device median J Surg. PubMed Scopus Google A.J. et in advanced heart failure patients with left ventricular assist devices for Heart PubMed Scopus Google Scholar The rates of pump infections were reported in 3 studies with the number of included patients ranging from to studies, the incidence ranged from to over a follow-up of months to years. infections were the most commonly studied infections (n = studies with number of patients ranging from to IQR, for infections within the first 1 month ranged from to C. Pagani F.D. M.S. et outcomes after implantation of a left ventricular assist device and PubMed Scopus Google M. E. D. et and of patients with a HeartMate II left ventricular assist device to the Scholar to within the first 6 months of L.W. Pagani F.D. Russell S.D. John R. Boyle A.J. Aaronson K.D. et al.Use of a continuous-flow device in patients awaiting heart transplantation.N Engl J Med. 2007; 357: 885-896Crossref PubMed Scopus (1343) Google G. P. A. M. HVAD clinical experience with a left ventricular assist device with a in a Heart Lung Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar and and within 1 year of Y. M. S. S. S. R. et outcomes with left ventricular assist devices in a country with a heart initial outcomes with Heart 2016; PubMed Scopus Google T. B. et experience of patients with a continuous-flow left ventricular assist clinical and after J Surg. PubMed Scopus Google Scholar for were reported in 6 studies, with the number of included patients ranging from to (median, IQR, The incidence of ranged from to was reported in 2 studies, with the number of patients of to and reported rates of to infections were reported in studies, with studies; urinary tract infections studies; and report rate for entire cohort at and the most A rate for infections was reported in studies. studies reported the with the most common studies) followed by studies). The of this scoping review was to an of the literature infections among patients with contemporary This study identified a total of 132 between 2007 and with an increased annual of published studies over a of studies did not report to the Reporting of Studies in including demographic information or follow-up E. M. et al.The the reporting of observational studies in guidelines for reporting observational Med. 2007; PubMed Scopus Google Scholar Although the majority of studies were conducted in the United the of study locations the global of infections related to LVAD studies in infection definitions as well as reporting by type and of infections (Figure The increased annual LVAD infections the increased use of continuous-flow LVAD in to than in E.J. Shah P. Kiernan M.S. Cornwell III, W.K. Copeland H. Takeda K. et al.The Society of Thoracic Surgeons Intermacs 2020 annual report.Ann Thorac Surg. 2021; 111: 778-792Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Despite in with and devices, this literature the persistent of postimplant analysis from the of in Circulatory Support HeartMate 3 trial that from infection is between the HeartMate II and HeartMate L. B. John R. et ventricular assist and a analysis of the 3 Heart Lung Transplant. Full Text Full Text PDF PubMed Scopus Google Scholar a lack of to minimum reporting criteria limited the to the studies, with and race reported in of 3 studies. although of studies reported follow-up duration, the type of follow-up information reported with different studies reporting number of median number of or Studies in reporting follow-up duration for the study cohort or for although the number of infections in LVAD recipients has increased over this review identified in the patient from data were the 132 studies there were only 72 unique patient This in the published literature generalizability of the of studies. there was variability in postimplant infections were To the reporting of infections within the of LVAD, ISHLT published a in M.M. Husain S. Mattner F. Danziger-Isakov L. Drew R.J. Corey G.R. et al.Working formulation for the standardization of definitions of infections in patients using ventricular assist devices.J Heart Lung Transplant. 2011; 30: 375-384Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar Although the of this was in to of outcomes studies, only of the 132 studies in this report to ISHLT the Circulatory Support has published a with adverse event Cowger Kirklin J.K. et definitions of adverse for and of mechanical circulatory support: a of the mechanical circulatory support research Heart Lung Transplant. Full Text Full Text PDF PubMed Scopus (12) Google Scholar The lack of standardization in reporting limits the to infection rates as well as identify of This is pertinent with to for LVAD, a for randomized of are not and are from observational studies after the initial clinical Results of this review that most research studies on reporting LVAD-specific infections, and most driveline and infections are the most commonly infections in this and are associated with an increased risk of and P. Birk S.E. Cooper L.B. Psotka M.A. Kirklin J.K. Barnett S.D. et al.Stroke and death risk in ventricular assist device patients varies by ISHLT infection category: an INTERMACS analysis.J Heart Lung Transplant. 2019; 38: 721-730Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar LVAD-specific infections are to during the postimplant follow-up and infections are to after M.M. Xie R. Cowger J. Schueler S. de By T. Dipchand A.I. et al.Epidemiology of infection in mechanical circulatory support: a global analysis from the ISHLT Mechanically Assisted Circulatory Support Registry.J Heart Lung Transplant. 2019; 38: 364-373Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar There are several factors to LVAD recipients that them to infections, including a large burden of as well as and or M.M. Husain S. Mattner F. Danziger-Isakov L. Drew R.J. Corey G.R. et al.Working formulation for the standardization of definitions of infections in patients using ventricular assist devices.J Heart Lung Transplant. 2011; 30: 375-384Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar Accordingly, studies at and infections are The of this scoping review should in the of several Studies with than 10 patients were from for this review. Although this have studies, studies not have provided of infection Although this search was limited to studies, there were no and the exclusion of language studies is as a within scoping review methodology to and H. L. Scoping a methodological J Res Methodol. Scopus Google Scholar In accordance with scoping reviews, the reported did not include data from published abstracts (eg, from at scientific abstracts focused on G. Y. A. M. et scoping review of between abstracts and full in Med Res Methodol. 2017; PubMed Scopus Google Scholar This scoping review studies the rates of infections in LVAD recipients, and a that the published literature studies that not to minimum reporting criteria and not use standardized definitions of The results of this review have several for future should authors to report infections in accordance with standardized definitions (eg, to scientific rigor and of outcomes studies. studies have focused on LVAD-specific infections, driveline infection, in a lack of scientific among the commonly and Accordingly, research studies to standardized definitions are to advance the scientific rigor of this

Topics & Concepts